The current epidemic of the severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, SARS-CoV. To date, the global confirmed SARS cases have reached >8,000 with L800 deaths in 30 countries. With an ease of transmission and severity of the disease, SARS poses a great threat to public health and causes significant economic loss. The long-term goal of this proposed research is to develop an efficacious vaccine for preventing future SARS epidemic. While various types of vaccines have been developed for different illnesses, current information obtained from studies on animal coronaviruses and their respective hosts suggests that the most promising vaccine for SARS would be a coronavirus-based live vaccine. However, the development of an attenuated, live SARS-CoV vaccine is a long-term approach with an unpredictable outcome. Previously, the P.I. has isolated a human enteric coronavirus (HECoV) associated with acute, mild diarrhea but with no other severe clinical symptoms. Based on the tenet of a common mucosal immune system, antigenic stimulation by oral immunization is usually very effective in inducing immunity to respiratory pathogens. Therefore, the P.I. proposes (i) to develop a recombinant human enteric coronavirus expressing the spike protein of the SARS-CoV as a vaccine for SARS, and (ii) to characterize the biological properties of the recombinant coronavirus. These studies can be accomplished within the proposed, short period of time and will provide crucial information about the utility of the recombinant coronavirus as an expression vector and as a candidate live vaccine for SARS. They will facilitate future clinical trials in animals and humans. Such a recombinant system will not only be important for the development of SARS vaccine but may provide potential avenues for the development of vaccines for other severe infectious diseases such as AIDS. It also provides a powerful molecular tool for studying pathogenesis and immunity of SARS-CoV. The practical impact of this research will be undoubtedly enormous. This research thus represents the exploratory nature of the R21 mechanism.